Anatomy and retrograde connectivity of the septal nuclei in the Göttingen minipig

Abstract

The basal forebrain septum separates the lateral ventricles and comprises the septum pellucidum and septum verum, the latter containing the septal nuclei. These nuclei are involved in cognitive, emotional, and autonomic function and are implicated in psychiatric and neurological disorders, including Alzheimer’s disease. However, their detailed organization and connectivity remain insufficiently characterized in translational large‑animal models. In the present study, we investigated the anatomy and connectivity of the septal nuclei in the Göttingen minipig. Brain tissue was processed using Nissl staining and choline acetyltransferase immunohistochemistry, and neuronal connectivity was examined using magnetic resonance imaging‑guided stereotaxic tracer injections. The septum comprises medial, lateral, posterior, and ventral complexes with distinct cytoarchitectonic features. Cholinergic neurons were primarily located within the medial septal complex. Both medial and lateral septal nuclei received widespread afferent projections from cortical, limbic, diencephalic, and brainstem regions, including the hippocampus, amygdala, hypothalamus, thalamus, ventral tegmental area, and periaqueductal grey. The medial septal nuclei showed relatively stronger inputs from prefrontal cortical regions, whereas the lateral septal nuclei received more prominent projections from brainstem structures. Reciprocal intrinsic connections within the septal region were also observed. These findings extend current knowledge of septal organization in the Göttingen minipig and support its use as a model for studying septal circuitry and related disorders.